Preparation of alpha - hydroxylamino lactams by hydrogenation of alpha-nitro lactams

ABSTRACT

A-NITROLACTAMS CAN BE CATALYTICALLY HYDROGENATED USING PALLADIUM-ON-CHARCOAL CATALYST TO AFFORD C5-C12 A-HYDROXYLAMINO LACTAMS WHICH ARE NOVEL COMPOSITIONS OF MATTER. THESE A-HYDROXYLAMINO LACTAMS HAVE BIODYNAMIC PROPERTIES, INCLUDING HERBICIDAL, INSECTICIDAL, FUNGICIDAL, AND ACARICIDAL. ADDITIONALLY, THEY ARE USEFUL AS TRANSITION METAL CHELATING AGENTS. THEY CAN ALSO BE OXIDIZED TO OXIMINO LACTAMS WHICH ARE KNOWN CHELATING AGENTS.

United States Patent 01 lice 3,567,711 Patented Mar. 2, 1971 3,567,711PREPARATION OF oz HYDROXYLAMINO LACTAMS BY HYDROGENATION F 0:- NITROLACTAMS Jan Frans Van Peppen, Chester, N.J., assignor to Allied ChemicalCorporation, New York, N.Y. No Drawing. Filed Sept. 30, 1969, Ser. No.862,514 Int. Cl. C07d 41/06 U.S. Cl. 260-2393 9 Claims ABSTRACT OF THEDISCLOSURE a-Nitrolactams can be catalytically hydrogenated usingpalladium-on-charcoal catalyst to afford C -C a-hydroxylamino lactamswhich are novel compositions of matter. These d-hYdIOXYlBIIllHO lactamshave biodynamic properties, including herbicidal, insecticidal,fungicidal, and acaricidal. Additionally, they are useful as transitionmetal chelating agents. They can also be oxidized to oximino lactamswhich are known chelating agents.

BACKGROUND OF THE INVENTION This invention relates to a novel class ofcompounds, specifically to a-hydroxylarnino lactams of the structure:

wherein n ranges from 3 to 10, and to a process for producing suchcompounds by the catalytic hydrogenation (reduction) of a-nitrolactams:IITOz 2 052).. 0:0 H

tionally, the rat-hydroxylamino lactams of the instant in- V ventionhave been found to possess herbicidal, insecticidal, fungicidal, andacaricidal activity.

Lactams of 5 to 12 carbon atoms are all compounds Well known to theprior art. caprolactam, which has 6 carbon atoms and the dodecyl (Clactam, for example, are produced in multimillion-pound quantitiesannually for transformation into nylon 6 and nylon 12, respectively. TheC to C Ot-Illtl'O caprolactams are produced by phosgenation and thennitration of the lactams as reported, for example, in British Pat. No.901,169 and in U.S. Pat. No. 3,093,365.

The prior art has, however, never reported the preparation of anytat-hydroxylamino lactams either by reduction, i.e., catalytichydrogenation of the known oc-HitI'O lactams, or by any other method.

The failure of prior-art workers to prepare the whydroxylamino lactamsby reduction of the corresponding a-nitro compound is doubtless owing tothe fact that ordinary catalytic hydrogenation methods, when applied toan a-nitro lactam, afford either the fully reduced a-amino lactam or amixture thereof with the partially reduced tat-hydroxylamino lactam. Forexample, U.S. Pat. No. 3,048,580 reports the essentially quantitativereduction of a-nitrocaprolactam to a-amino caprolactam usingpalladium-on-carbon catalyst.

The prior art does teach certain catalytic hydrogenation methods forreducing nitro-normal and cycloalkanes to the correspondinghydroxylamino alkanes. Unfortunately, in catalytic hydrogenation, theconfiguration and polarity of the molecule being reduced is of crucialsignificance in determining the course of the partial hydrogenation of afunctional group which is substituent on such molecule. Hence, methodssuitable for reducing nitroalkanes to the corresponding hydroxylaminocompound would not be expected to be suitable for nitro lactams.

U.S. Pat. No. 2,829,163 teaches the reduction of nitrocyclohexane tohydroxylamino cyclohexane by catalytic hydrogenation in an equimolar 10%aqueous acetic acid solution at 20 C. using palladium-on-aluminacatalyst.

Meister et al. (Ann. Chemie, 674, 83, 1964, at 89, and U.S. Pat. No.2,886,496) describe the catalytic reduction of nitrocyclododecane tohydroxylamino cyclododecane using as catalyst palladium on varioussupports.

U.S. Pat. No. 3,393,237 describes the reduction of nitrocyclohexane tocyclohexylhydroxylamine by the use of palladium on carbon treated withan amine selectivity agent. However, even if it is eflfective suchselectivity agent is a product contaminant and requires removaltherefrom.

I have found the procedures described in these references are unsuitablefor the partial reduction of a-nitro lactams.

An article by Guyer and Merz [Chimia, 18, 144 1964)], teaches thereduction of nitrocyclohexane to hydroxylamino cyclohexane usingpalladium on carbon in aqueous hydrochloric acid at room temperature.Such a method would, of course, be unsuitable to reduce a-nitrolactams,since the acid would cause opening of the lactam ring.

U.S. Pat. No. 2,967,200 teaches that reduction of nitrocyclohexane andother nitroalkanes using palladium-oncarbon gives mainly the amine plussome oxime. When poisoned with lead compounds, the oXime is the majorproduct.

British Pat. No. 797,985 describes the catalytic reduction ofnitrocycloalkanes to cycloalkyl oximes using palladium-on-carboncatalyst modified by treatment with a lead salt.

It is thus apparent that the prior art workers not only had neverprepared (at-hydroxylamino lactams, but also were unaware of a simple,straightforward rapid method that would clearly be applicable to suchpreparation. Specifically, the prior art did not teach a rapid catalyticmethod suitable for transforming whydroxylamino lactams essentiallyuncontaminated with side products.

SUMMARY OF THE INVENTION It is an object of this invention to provide anovel class of compounds, specifically C to C tat-hydroxylamino lactamsthat are useful as chelating agents and that also have valuablebiodynamic properties.

It is a further object of this invention to provide a catalytic processfor preparing such a-hydroxylamino lactams from readily availablestarting materials, i.e., the tat-nitrolactam of the same number ofcarbon atoms.

'Further objects and advantages will become apparent from thedescription of the invention which follows in greater detail.

These and other objects are accomplished according to our inventionwherein C to C a-nitrolactams are catalytically reduced tou-hydroxylaminolactams.

The preferred nitrolactam is tat-nitrocaprolactam because of thecheapness and ready availability of the starting materialcaprolactamfrom which the nitrolactam is prepared as previously described.

The catalyst useful in the reduction, i.e., hydrogenation, process ofthe instant invention is palladium on charcoal, also referred to aspalladium on active carbon. The preparation of such palladium-on-carboncatalyst is well known in the art. Such preparation is described, forexample, in Organic Synthesis, vol. 3 (1955), at pp. 385 and 685.Suitable catalyst is sold by Baker and Co., Newark, N.J., USA.

I have found the weight ratio of palladium to carbon is not particularlycritical since the carbon serves merely as a support for the palladium,which is the active catalyst constituent. Ordinarily, from 0.l10.0weight percent palladium on carbon is suitablepreferably 2.0-6.0 Weightpercent. A suitable palladium-to-nitrolactam ratio can vary over widelimits depending upon the reduction time and other reduction conditionsdesired. Ordinarily, a nitrolactam-to-palladium weight ratio of fromabout 50:1 to about 100021 is suitablepreferably 100:1 to 500:1.

A suitable hydrogenation temperature is from about 20 to 80 0.,preferably about 50-70 C. Temperatures below 20 C. do not give suitablehydrogenation rates coupled with adequate selectivity. By adequateselectivity is meant that the nitrolactam is reduced essentiallycompletely and exclusively to the hyldroxylamino lactam. Above about 80C. significant quantities of undesirable further reduction products,e.g., aminolactam, are obtained.

Since the a-nitrolactams are solids, the hydrogenation is mostadvantageously carried out on a solution or partial solution of thetat-nitrolactam in an organic solvent. By partial solution is meant thatsufiicient solvent is present to dissolve at least about 10% of thenitrolactam at the hydrogenation temperature. As the dissolvednitrolactam is reduced, more nitrolactam will be dissolved and thenreduced. Preferably, sufficient solvent is present to completelydissolve all the nitrolactam at the hydrogenation temperature. Since thehydroxylamino lactam is ordinarily more soluble than the nitrolactam,sufficient solvent to dissolve all the nitrolactam at the hydrogenationtemperature is generally also sufficient to dissolve the hydroxylaminolactam product at room temperature, which is desirable in that itfacilitates separation of the product from the palladium-on-carboncatalyst following hydrogenation.

The chemical nature of the hydrogenation solvent is not critical; it isessentially subject to only onelimitation that is the solvent must beinsert, i.e., it should not react with either the reactant or theproduct and, of course, not be itself subject to hydrogenation under theprevailing conditions. Preferably the solvent is sufi'iciently misciblewith Water to form a homogeneous phase With the water produced duringreduction. Preferably also. the

4 nitrolactam should be soluble therein to the extent that at leastabout 10% of the hydrogenation temperature. Most preferably, both thenitrolactam and the hydroxylamino lactam will be soluble to a greaterextent so as to facilitate the recovery of the hydrogenation product andeliminate the need for handling large volumes of solvent.

The hydrogenation solvent is preferably a C -C alcohol, e.g., methanol,ethanol, nor isopropanol, t-butanol, or a mixture thereof, which alcoholcan be anhydrous or can contain up to about 50 volume percent water.Most preferably the solvent is ethanol containing 10 to 50 volumepercent water.

Most conveniently, catalyst, nitrolactam and solvent are added to apressure vessel and the nitrolactam dissolved in the solvent by shakingand mild heating. The vessel is then purged of air and sufficienthydrogen introduced to provide a pressure of 15-2000 p.s.i.g. at thedesired hydrogenation temperature, i.e., 2080 C. The vessel and itscontents are then heated to, and maintained at, the desired temperature,preferably with simultaneous agitation achieved, e.g., by stirring, orby shaking or rocking the vessel. Hydrogenation is ordinarily completein from about 10 to 200 minutes and is indicated by a substantialdecrease or cessation in the rate of hydrogen uptake. If desired,hydrogen can be introduced continuously during the reduction reactionuntil 2 mols of hydrogen has been utilized per mol of nitrolactam.

The reaction can be represented as follows:

The vessel is then cooled to room temperature and vented. The reactionmixture is then filtered or decanted to separate thepalladium-on-charcoal (carbon) catalyst and the filtrate, which consistsof the hydroxylamino lactam product, solvent and one mol of water perone mol of nitrolactam formed in the reduction, then evaporated toafford crude hydroxylamino lactam as a residue. If desired, this residuemay be further purified by recrystallization from a solvent such asmethanol, water, or a mixture thereof.

The invention can be more fully understood by reference to the followingexamples. All parts are parts by weight unless otherwise expresslynoted.

EXAMPLE 1 A solution of 3.16 grams (20 millimols) of nitrocaprolactam in200 ml. of 40% aqueous acetic acid solution was hydrogenated using 0.316gram of 10% palladium-onalumina catalyst. The hydrogenation temperaturewas 2629 C. and the hydrogen pressure varied from 30 to 60 p.s.i. duringhydrogenation with additional hydro-.

gen being added to replace that which was used up in the reductionreaction. After 15 minutes, hydrogen uptake was 25 millimols. Thereaction was stopped at this point, the catalyst removed by filtration,and the product analyzed by thin layer chromatography and titrationwhich indicated that the reaction product contained approximately 4.9millimols of OC-hYdI'OXYIaIIIIHO caprolactam, 4.4 millimols ofa-oximinocaprolactam, and 2.5 millimols of rx-amino caprolactam, plusunreacted nitrocaprolactam and other unidentified products. It is thusapparent that even a large excess of 40% aqueous acetic acid will nottrap the desired hydroxylamino intermediate reduction product andthereby prevent the formation of further products when using thiscatalyst.

catalyst consisting of 0.316 gram of 5% palladium on calcium carbonate.Hydrogenation temperature was 40 F C. and the hydrogen pressure wasmaintained at 50-60 p.s.i. during hydrogenation. After 174 minutes, 12.9millimols of hydrogen had been consumed and replaced by addingadditional hydrogen. The reaction was terminated at this point and theproduct analyzed by thin layer chromatograph and titration. The reactionproduct was indicated to be a mixture containing about 3.1 millimols ofhydroxylamino caprolactam, 1.8 millimols of u-oximino caprolactam and0.3 millirnol of a-amino caprolactam.

EXAMPLE 3 A solution of 3.16 grams nitrocaprolactam in 80 ml. of ethanolwas hydrogenated over 0.316 gram of 1% palladium on alumina at 20 C. and60 p.s.i.g. hydrogen pressure for a period of 17 hours. A total of 40.1millimols of hydrogen was consumed and was replaced. Thin layerchromatography and titration of the product indicated it to be a mixturecontaining approximately 13.2 millimols rat-hydroxylaminocaprolactam,4.5 millimols aoximino caprolactam and 2.5 millimols a-aminocaprolactam.

EXAMPLE 4 The reduction was carried out as in Example 5 except thecatalyst was 1% palladium on calcium carbonate and the hydrogenation wascarried out for 18 hours. Thin layer chromatographic analysis andtitration of the product showed it to be a mixture containing 3.5millimols a-oximino caprolactam, 6.9 millimols a-aminocaprolac tam, 6.1millimols a-hydroxylaminocaprolactam and 3.5 millimolsa-nitrocaprolactam.

EXAMPLE 5 To 3.16 grams (20 millimols) of nitrocaprolactam in 70 ml. ofethanol in a pressure vessel was added ml. of n-butylamine and 0.316gram of 5% palladium on charcoal. The mixture was heated to 60 C. undernitrogen and the nitrogen then replaced with hydrogen at 65 p.s.i.g. Thevessel was then sealed and agitated for 47 minutes. After venting,decantation from the catalyst, and stripping off the ethanol andbutylamine, the product was analyzed by thin layer chromatography andshown to contain approximately equal amounts of rat-hydroxylaminocaprolactam and u-amino caprolactam, thus indicating the ineffectivenessof amine selectivity agents on the reduction of nitrocaprolactam withpalladium on charcoal.

EXAMPLE 6- A solution of 3.16 grams millimols) of a-nitrocaprolactam in80 ml. of anhydrous ethanol was hydrogenated using 0.316 gram of 5%palladium-on-carbon catalyst in a Parr hydrogenation apparatus at C.Hydrogenation was carried out by pressuring the Parr vessel containingthe palladium-on-carbon catalyst and nitrocaprolactarn to 60 p.s.i. withhydrogen at ambient temperature and then heating the vessel and thecontents thereof to 40 C. with concomitant agitation. The pressurefluctuated between being admitted periodically to replace that which hadbeen taken up by reaction. Hydrogen uptake was complete after about 40minutes. The reaction mixture was removed from the Parr vessel, thecatalyst removed by filtration, and the reaction solution analyzed bythin layer chromatography.

The chromatographic analysis indicated that the predominant reactionproduct was a-hydroxylamino caprolactam. Very small amounts of u-aminocaprolactam and oc-OXlIIllIlO caprolactam were also present. Allnitrocaprolactam had been reduced.

EXAMPLE 7 A solution of 31.6 grams (200 millimols) of nitrocaprolactamin 800 ml. of 50% aqueous ethanol was hydrogenated using 3.16 grams of5% palladium-on-carbon catalyst. The hydrogenation temperature was 64 C.The pressure was maintained through the hydrogenation at 50-60 p.s.i.Hydrogen uptake ceased after 11 minutes of gentle agitation at theabove-indicated temperature. The reaction mixture was filtered to removecatalyst and the solvent removed by evaporation at rcduced pressure. Asyrupy residue remained. This residue was analyzed by thin layerchromatography which indicated the presence of 175 millimols ofhydroxylamino caprolactam and 4.7 millimols of amino caprolactam. Thehydroxylamino caprolactam was recovered by stirring the residue for onehour at room temperature with 200 ml. of glyme (1,2-dimethoxy ethane).This stirring procedure resulted in crystal formation. Recovery of thecrystals by filtration afforded 21.5 grams of hydroxylamino caprolactamwhich melted after recrystallization at ISO-152 C.

EXAMPLE 8 A series of wnitrolactams were reduced using the followinghydrogenation conditions. 10 g. of nitrolactam was dissolved in 250 ml.of 70% aqueous ethanol, and the solution placed in a glass pressurevessel. 1.0 g. of 5% palladium on charcoal was added and the vessel thensealed, degassed, and a hydrogen atmosphere introduced. The vesselcontents were then heated to 65 C., additional hydrogen introduced toprovide a hydrogen pressure of 100 p.s.i.g. and the vessel agitateduntil there was no significant further drop in hydrogen pressure. Thevessel was then vented, the catalyst filtered off and the filtrateevaporated at reduced pressure. Thin layer chromatographic analysis ofthe evaporation residue indicated in all cases that:

(1) No oc-IlitIO compound was present. (2) The u-oximino compound waseither completely absent or present only in trace amounts.

(3) The major product was the desired tit-hydroxylamino lactam with aminor product being a-aminolactam. (4) The u-amino lactam never amountedto more than 7% mol based on rat-hydroxylamino lactam.

The following a-nitrolactams were reduced:

a-nitrovalerolactam a-nitrocaprylalactam u-nitro aurolactam The resultsof the above experiments indicate that only palladium-on-charcoal iscapable of reducing a nitrolactams to rat-hydroxylamino lactams withoutthe production of significant amounts of side reduction products.

I claim:

1. A process for producing an a-hydroxylamino lactam of the structurewherein n is 3 to 10, which comprises contacting a solution ofu-nitrolactam of the structure r CH and. o=o

wherein n is as defined above, in an inert solvent in the presence of0.1 to 10 wt. percent palladium-on-charcoal catalyst, wherein the weightratio of a-nitrolactam to palladium ranges from about 50:1 to l000:1,with hydrogen at a pressure of 15 to 200' p.s.i.g. at a temperature of15 to C. for a time sufficient to effect reduction of said a-nitrolactamto said d-hYdI'OXYlHJTlll'lQ lactam.

2.. A process in accordance with claim 1 wherein said catalyst is 2.0 to6.0 weight percent palladiurn-on-charcoal.

3. A process in accordance with claim 1 wherein said nitrolacta-m topalladium weight ratio is :1 to 500:1.

4. A process in accordance with claim 1 wherein the temperature is 50 C.to 70 C.

5. A process in accordance with claim -1 wherein the solvent is a C to Calcohol or mixture thereof with up to 50 volume percent Water.

6. A process in accordance with claim 5 wherein the solvent is ethanolcontaining 10 to 50 volume percent Water.

7. A process in accordance With claim 1 wherein said u-nitrolactam isu-nitrocaprolactam.

'8. A compound of the structure Nl-IOH CH onnn 0:0

wherein n is 3 to 10.

9. The compound of claim 8 which is whydroxylamino caprolactam.

References Cited UNITED STATES PATENTS 3,048,580 8/1962 Ottenheym et a1.260239.3

HENRY R. JILES, Primary Examiner 10 R. T. BOND, Assistant Examiner Po-wwUNITED STATES PATENT OFFICE (5/69) CERTIFICATE OF CORRECTION Patent No.3,567,711 Dated March 2 1221 invenwtol-(s) Jan Frans Van Peppen It iscertified that error appears in the above-identified patent and thatsaid Letters Patent are hereby corrected as shown below:

Claim 1, column 6, line 66, "200" should be --2ooo--;

and

"15" shouid be --20--.

Signed and sealed this lhth day of March 1972.

(SEAL) Attest:

EDWARQ M.FLETCH.bJR,JR. ROBERT GOTTSCHALK Atbestlpg Officer Commissionerof Patents

